Block 6: Functional Groups II Flashcards
1
Q
How does ethanol act as a base?
A
CH3CH2OH + Na+NH2- –> CH3CH2O-Na+ + NH3
2
Q
How does ethanol act as an acid?
A
CH3CH2OH + H2SO4 —> CH3CH2OH2 + HSO4-
3
Q
What is the conjugate base of an alcohol called?
A
An alkoxide ion
4
Q
What is the conjugate acid of an alcohol called?
A
An oxonium ion
5
Q
Why are the alkoxide and oxonium ions important?
A
They act as EXCELLENT nucleophiles and electrophiles in the synthesis of organic compounds
6
Q
Are phenols acidic or basic?
A
Phenols are vaguely acidic as their conjugate base in an electron donating group, causing the ring to become resonance stabilized.
7
Q
How do electron withdrawing groups affect the acidity of a phenol?
A
They make it more acidic as they stabilize the phenoxide anion further
8
Q
How do electron donating groups affect the acidity of a phenol?
A
They make it less acidic as they destabilze the phenoxide anion
9
Q
How do you know whether an alcohol will react via Sn1 or Sn2?
A
Same rule as for haloalkanes
10
Q
How can alcohols be prepared?
A
Alkyl Halide Hydrolysis Acid catalysed addition of H2O Hydroboration-oxidation Reduction of aldehyde/ketone/ester Grignard reagents with Methanal, other aldehydes, ketone, esters or acyl chlorides.
11
Q
What is the mechanism of an alcohol being formed via alkyl halide hydrolysis?
A
CH3Br + OH- –> CH3OH + Br- (Sn2)
(CH3)3CCl +H2O –> (CH3)3C+ +Cl –H2O–> (CH3)3CO+H2 — -H –> (CH3)3COH + HCl
12
Q
What is the mechanism of an alcohol being formed via acid catalysed addition of H2O?
A
CH3CH=CH2 + H2O —(H+) –> CH3CH(OH)CH3 + CH3CH2CH2OH
13
Q
What reagent do you use if you want the minor product of an addition reaction with alcohol?
A
B2H6/OH-
14
Q
What is the mechanism of an alcohol being formed via hydroboration oxidation?
A
CH3CH=CH2 —(B2H6/H+)–> CH3CH2CH2BrH2 —> CH3CH2CH2OH
15
Q
What does an aldehyde reduce to?
A
Primary aclohol
16
Q
What does a ketone reduce to?
A
Secondary alcohol
17
Q
What does an ester reduce to?
A
2x primary aclohols
18
Q
What are the reagents you could use to reduce an aldehyde/ketone/ester?
A
LiAlH4 or NaBH4 with H3O+
19
Q
What is formed when methanal reacts with a grignard reagent?
A
Primary alcohol with an extra carbon
20
Q
What is formed when an aldehyde other than methanal reacts with a grignard reagent?
A
Secondary aclohol
21
Q
What is formed when a ketone reacts with a grignard reagent?
A
Tertiary alcohol
22
Q
What is formed when an ester or acid chloride reacts with a grignard reactant?
A
A tertiary alcohol is formed with 2 identical R groups.
23
Q
What are the ways in which new C bonds can be formed?
A
Grignard reagents, nitriles, and alkynides (Grignard most likely)
24
Q
What are the reactions an alcohol can perform?
A
Substitution
Elimination
Oxidation
25
What reagents are needed for an alcohol to form a haloalkane?
Addition of SOCl2 (if primary or secondary) or HCl (if tertiary)
26
What is the mechanism of Sn1 and Sn2 alcohol substitution?
CH3OH --(SOCl2) --> CH3Cl
| (CH3)3COH + HCl --> (CH3)3CCl + H2O
27
What reagents are needed for an alkoxide to form an ether?
CH3CH2O- + RX --> CH3CH2COR + X-
28
What reagent is needed to form an alkene from an alcohol?
Concentrated H2SO4 and Heat.
29
Why does the alcohol have to be protonated (unlike the haloalkane) to form an alkene?
Because OH on its own is a poor leaving group, but H2O is very good.
30
What is the mechanism of a tertiary alcohol becoming an alkene?
CH3CH2OH --->H3O+/Heat---> CH3CH2OH2+ ---> CH3 CH2+ +H2O ----> CH2=CH2
31
What is the mechanism of a 1/2 alcohol becoming an alkene?
CH3CH2OH + H2O---> transition state with a bond breaking between H anc C and C and OH2+, with a bond forming between H and OH and C and C
32
What do primary alcohols form when they are oxidised with H2CrO4?
Carboxylic acids
33
What to primary alcohols form when they are oxidised with PCC?
Aldehydes
34
What do secondary alcohols form when they are oxidised with H2CrO4?
Ketones
35
How are ketones formed on a ring structure?
Acid chloride + AlCl3 ---> Ph-COCH3 + HCl
36
How do A/K undergo nucleophilic addition? (general)
RCOR + Nu- ---> RC(O-)NuR --- (H+) ---> RC(OH)NuR (Only works with strong nucleophile)
37
What is a second way for A/K to undergo nucleophilic substitution?
RCOR + H+ ---> RCOHR +Nu-H ----> RC(OH)Nu-H)R --- (-H+) --> RC(OH)NuR
38
What does the oxonium ion method of a/k substitution require?
A weak nucleophile with an Nu-H bond.
39
How does the rate of reaction for a/k nucleophilic substitution change depending on the carbonyl's R groups?
2Hs = fast
1H 1Alkyl/aryl = between
2alkyl/aryl = slow
40
Why does the trend in reaction rate for a/k substitution exist?
This is due to the electronic and steric effect changing the size of the delta +/- charges.
41
What is the reagent needed for an a/k to react with cyanide?
-CN/H3O+
42
What is the mechanism for an a/k reaction with -CN?
RCOR + -CN --> RCO(-)CNR --> RC(OH)CNR ----(H3O+) RC(OH)COOHR
43
What are possible oxygen nucleophiles that can be added to an a/k?
H2O, ROH
44
What is the reaction of an a/k reacting with water?
RCOR + H2O --> RC(OH2)R
45
What should be remembered about an a/k reaction with water?
Alkehydes favor the products more than ketones due to H2O being a good leaving group
46
What is the mechanism of an a/k reaction with an alcohol?
1. RCOR + H+ --->RCOHR + ROH --> RC(OH)(OHR+)R --- (-H) RC(OH)(OR)R (Called a hemiacetal)
2. RC(OH)(OR)R + ROH ---> RC(OR)2R +H2O (called an acetal)
47
Why are acetals important?
They serve as 'protecting groups' in the synthesis of some molecules
48
What are some nitrogen nucleophiles which a/ks could react with?
RNH2
NH2OH
H2NNH2
49
What is the mechanism for an a/k reaction with a nitrogen nucleophile?
RCOR + R'NH2 RC(OH)(NH2R'+)R ---(-H2O)--> R(C=NR')R
50
What is RC(NR)R called?
An imine
51
What is RC(NOH)R called?
An oxime
52
What is RC(NH2)R called?
A hydrazone
53
How do you remember what reagent to use when forming a compound using a nitrogen reagent?
It's always (whatever you want) attached to an NH2 group.
54
What is an alpha carbon?
A carbonyl carbon
55
What is the requirement for a carbonyl to form an enol or enolate?
It must have an H on a vicinal C to the alpha carbon
56
How does a carbonyl carbon form an enol?
CH-C=O + HB ---> (Sn2 transition state) C=COH + HB
57
How does a carbonyl carbon form an enolate?
CH-C=O + B- ---> C=CO- + HB
58
Which is more useful out of an enol and enolate?
Enolate as it's negatively charged and so way more reactive and useful for synthesis.
59
How is the enolate anion stabilised?
It can delocalise its charge to the vicinal Carbon
60
Why is an enol difficult to isolate?
It exists almost entirely in its ketone form (more stable)
61
Why do enols spend almost all their time in keto form?
The C=O bond is stronger than the C=C bond, making it more stable
62
What does tautomerisation mean for the isolation of an enolate anion?
A strong base is needed (OH-, RO-, NH2- or H-)
63
What can enols and enolates be used for?
Alkylation reactions- joining of an R group.
64
How does alkylation proceed when acid catalysed?
An RX + the enol causes the R to join to the double bond, and the O double bond to reform. This causes the R group to join the alpha carbon and a carbonyl carbon, with expulsion of HX.
65
How does alkylation proceed when base catalysed?
An RX + an enolate cause the R to join the double bond, and the O double bond to reform. This causes the R to join the alpha carbon and a carbonyl carbon, with expulsion of X-.
66
Which is better and why- acid or base catalysed alkylation?
Base catalysed as the enolate is more reactive than the enol.
67
How does an aldol form?
A base removes the alpha hydrogen from a carbonyl compound, forming a carbanion. Following this, a second carbonyl reacts with the anion, and the negative carbanion carbon joins to the delta positive carbonyl carbon, forming a bigger structure. The negatively charged ex-carbonyl Oxygen then re-takes the hydrogen, forming an alcohol on one side joined to an aldehyde on the other- an aldol.
68
How does an aldol form an enal?
If the alcohol group neighbours a Carbon with a Hydrogen, these can react to come off, forming a double bond in their place- giving the final product as an enal.
69
What needs to be remembered about substituents on Carboxylic acids?
With substituents joined directly to acids in straight chained molecules, or ortho/para in aromatic acids, the acid's pKa is affected by whether the substituent is withdrawing or donating. If the directly attached atom of the substituent has a delta + charge it withdraws electrons, and those with lone pairs of electrons donate electrons.
70
Do electron donating groups increase or decrease acid strength?
They decrease the acid strength as larger alkyl groups push more electrons into an already negatively charged compound, destabilizing the ion and making it less likely to form.
71
Do electron withdrawing groups increase or decrease acid strength?
They increase acid strength as they have a slight delta plus charge, allowing them to absorb the negative charge and make a more stable resonance structure, making the ion more likely to form.
72
Do halogens on the alkyl substituent increase or decrease the acid strength?
Increase as they are highly electronegative, making the attached C even more positive and able to accept an electron.
73
Are acids or phenols more soluble in Hydrogencarbonate (acid) and why?
Acids are more soluble as the conjugate acid which is formed is weaker than the acid itself, so is more product favored. However, the phenol is a weaker acid than the potential conjugate, and so is not as soluble as the reaction is reactant favored.
74
What are the ways of preparing a carboxylic acid?
Oxidation of a primary alcohol/aldehyde
From a grignard reagent with CO2
From a nirile
75
How do you prepare a carboxylic acid from a grignard reagent and CO2?
R-MgX + CO2 ---> R-C=O(OMgX) --(H3O+)--> RCOOH
76
How do you make carboxylic acid from a nitrile?
R-X + -CN --> RCN + Br- --(H3O+)--> RCOOH + NH3
77
What are the derivatives of carboxylic acids?
Acid chlorides, Carboxylic acids, Acid Anhydrides, Esters and Amides
78
What is the process of substituting a carboxylic acid derivative?
RCOY + Nu- --> RC(Nu)(O-)Y --> RCONu + Y-
79
What is the reactivity order of carboxylic acid derivatives?
Acid Chlorides > Acid Anhydrides > Esters > Amides
80
What step is the slow step of the substitution of carboxylic acid derivatives?
The joining of the nucleophile
81
Why is the reactivity order the way it is?
As the breaking of the C-Y bond is the slow step, the reactivity has nothing to do with the leaving ability of Y. If the Y group is electron withdrawing, the C will be more positive, allowing it to be attacked more effectively by the nucleophile. However, if the group is electron donating it makes the C less positive, making it less reactive with a nucleophile.
82
How do you prepare an acid chloride?
RCOOH + SOCl2 --> RCOCl + HCl + H2O
83
What can acid chlorides form?
Acids (H2O), Amides (NH2R), Esters (ROH) and Anhydrides (RCOOH)
84
How do acid chlorides react with grignard reagents?
RCOCl ---(2R'MGX/H3O+)--->RC(R')2OH
85
What is an acid anhydride?
R-C=OOC=O-R
86
How is an acid anhydride formed?
- 2x Carboxylic acids with P2O5 form acid anhydride symmetrically with H2O
- Acid chloride with a carboxylate ion to form unsymmetrical acid anhydride and Hydrogen Chloride
87
How can acid anhydrides react?
Form an ester with an alcohol, amide with NH2R and a carboxylic acid with H2O
88
How is an ester formed?
Acid chloride + alcohol/phenol
Carboxylic acid + Alcohol
Acid anhydride + alcohol
89
How do esters react?
They are slower than acid chlorides or anhydrides.
They form amides with RNH2 and carboxylic acids with H2O in either acidic or basic conditions (to form a carboxylic acid and alcohol)
They can also be reduced to produce two primary alcohols, (the carbonyl side is always primary)
Finally, grignard reagents form a tertiary alcohol with two equivalent groups (using two equivalents of ester).
90
What biological application do esters have?
Polyesters are used to form stitches, which are broken down by the slight acidity of body fluids- thus forming dissolvable stitches.
91
How do you make amides?
From an acid anhydride, ester or acid chloride with RNH2
92
How do amides react?
They form RNH3+ and a carboxylate anion with H3O+ and heat, and further reaction of the RNH3+ with OH- forms RNH2
With H2O to form Acids
93
How do polypeptides form?
diacid chlorides and diamides form a peptide bond
94
Why are amides neutral, rather than basic?
The resonance from the double bond on O to the N reduces the availability of the electron pairs.
95
What are the seven types of reactions?
```
Electrophilic Addition
Nucleophilic Addition
Nucleophilic Substitution
Nucleophilic Acyl Substitution
Elimination
Oxidation
Electrophilic Aromatic Substitution
```
96
What are the three combinations of reactions?
Nucleophilic Addition with Nucleophilic Substitution
Nucleophilic Addition with Elimination
Nucleophilic Acyl Substitution with Nucleophilic Addition
97
What are some examples of electrophilic addition?
Alkene + H2/Pd OR X2 OR HX OR H2O/H2SO4
| Alkyne + Lindlar Catalyst OR Li/NH3/H3O+ OR H2/Pd OR X2 OR HX OR H2O/H2SO4
98
What are some examples of Nucleophilic addition?
C=O + NaBH4/H3O+ OR ROH/H+ OR CN-/H3O+ OR RMgX/H3O+
99
What are some examples of Nucleophilic substitution?
COH + HCl
| CX + OH- OR CN- OR C=_CR- OR OR-
100
What are some examples of Nucleophilic Acyl substitution?
C=OR + SOCl2 OR NH2R OR RCOOH OR ROH
101
What are some examples of elimination?
CHCX + OH-
CHCOH + H2SO4 conc
CXHCXH + OH-
102
What are some examples of Oxidation?
Alcohol --> Ketone/aldehyde/carb. acid
103
What are some examples of Nucleophilic addition + substitution?
Aldehyde/ketone to hemiacetal & acetal using (2)ROH/H+
104
What are some examples of nucleophilic addition + elimination?
Aldehyde/ketone to imine, hydrazone and oxine
105
What are some examples of Nucleophilic acyl substitution with nucleophilic addition?
Ester with LiAlH4 and H3O+ to form primary alcohols
| Ester/Acid chloride with 2RMgX?H3O+ to form a tertiary alcohol with two identical R groups
106
How are amines classed?
Primary, secondary or tertiary based on how many Cs there are bonded to the N
107
What are aromatic amines?
NR2 groups bonded directly to the benzene ring
108
Why are amines good nucleophiles or bases?
They have a lone pair of electrons on the N, and so are able to accept a proton
109
What can be used to determine the basicity of an amine?
The higher the pKa (weaker acid) the conjugate acid is, the stronger the basicity of the amine
110
What determines which class of amine is more basic and why? What is the trend?
Generally, the more R substituents on an amine, the more basic it is as the extra electron density on the N makes it more negative. However, a tertiary amine doesn't follow this pattern as the increased R groups make the compound more crowded, preventing it from gaining a proton as efficiently.
111
Why are aromatic amines much weaker than alkylamines?
The lone pair of electrons on N is donated into the ring, causing it to become resonance stabilized and less likely to react
112
What effect do electron withdrawing and donating groups have on an arylamine's basicity?
Electron withdrawing groups decrease basicity as they further stabilize the lone pair of electrons, making them less able to react as a base
Electron donating groups increase basicity as they add to the already negative charge, making it more concentrated and allowing N to act as a base
113
How are alkylamines prepared, but what is the issue with this?
They are prepared by substituting haloalkanes with NHR2 groups. However, each product is more reactive than the reactants, so you get a the produced CH3CH2NH2 reacing with the CH3CH2Br used to produce it. This results in a secondary amine, then tertiary, and eventually a quarternary ammonium salt. It is therefore not a good way of isolating amines, as a mixture results
114
How do arylamines form by subtitution?
By reacting Ph-NO2 with Fe/H+ and OH-, and NH2 group is substituted onto the ring, or an NHR or NR2 groups, if a 2ry or 3ry amine is requried.
115
How do amines form from reduction?
Reduction of a nitrile, primary amide, primary imine or oxime with LiAlH4/H3O+ results in a primary amine
Reduction of a secondary amide or an N-substituted imine results in a secondary alcohol
Reduction of a tertiary amide results in a tertiary bond
NB: The C with the original multiple bond always becomes a CH2 group!
116
How do amines react with halogens/acyl chlorides?
The reactions with haloalkanes are unstable, as mentioned in another card
Primary amines reacting with acyl chlorides form a secondary amide, while secondary amines form tertiary amides.
Tertiary amines cannot react with acid chlorides as they don't have a removable H.
117
How do primary arylamines react?
They form diazonium ions in the presence of HNO2 at 0 degrees celsius
118
Why are diazonium ions important?
They are intermediates in promoting the formation of meta substituted products, as they are meta directors which can be substituted after direction to form an o/p director. This allows the formation of a benzene ring with two o/p directors meta to one another
